Mass defect filter

Abstract

A method for detecting and identifying metabolites in biological samples includes subjecting the samples to high resolution mass spectrometry (MS) analysis to detect ions of the molecular species. Mass defect values for the detected ions are determined. The method also includes specifying a predetermined range for mass defect values. Detected ions having mass defect values falling outside the specified range are discarded and those with mass defect values falling within the predetermined range are retained. Species of interest are determined from the retained values. The species of interest include drug metabolites or impurities and/or degradants of a known pharmaceutical sample.

1. A method comprising the steps of:
 subjecting a biological sample to a high resolution mass spectrometry (MS) analysis;
 detecting the ionic masses of ions from said analysis, said ionic masses forming an initial mass range; 
 determining mass defect values for the detected ions in the initial mass range; 
 specifying a first range of mass defect values comprising a mass defect filter; 
 discarding detected ions having mass defect values outside the mass defect filter range; 
 retaining detected ions having mass defect values within the mass defect filter range; and 
 determining species of interest from the retained ions to detect and identify drug metabolites in the biological sample. 
 
 
     
     
       2. The method of  claim 1 , wherein the biological sample is one of plasma, bile, urine, fecal extract, bodily fluid or tissue sample. 
     
     
       3. The method of  claim 1 , wherein the sample subjected to MS analysis is first analyzed by a liquid chromatography (LC) system. 
     
     
       4. The method of  claim 1 , wherein the specified mass defect filter range is constant over the initial mass range. 
     
     
       5. The method of  claim 4  wherein the initial mass range includes all the mass defects determined for a data set. 
     
     
       6. The method of  claim 4  wherein the initial mass range includes a subset of all the mass defects determined for the data set. 
     
     
       7. The method of  claim 6  further comprising specifying a second mass defect filter range over another mass range, said other mass range being distinct from the initial mass range. 
     
     
       8. The method of  claim 7 , wherein the second mass defect filter range is constant. 
     
     
       9. The method of  claim 1  wherein the method is used to detect the presence of metabolites in the biological sample. 
     
     
       10. The method of  claim 1  wherein the method is used to detect the presence of impurities or degradants in the biological sample. 
     
     
       11. A method for detecting and identifying impurities in a drug sample, the method comprising the steps of:
 subjecting the sample to a high resolution mass spectrometry (MS) analysis to detect the ionic masses of ions in a chosen mass range; 
 determining mass defect values for detected ions in the mass range; 
 specifying a range of mass defect values comprising a first mass defect filter range; 
 discarding detected ions having mass defect values outside the first mass defect filter range; 
 retaining detected ions having mass defect values within the first mass defect filter range; and 
 determining species of interest from the retained ions. 
 
     
     
       12. The method of  claim 11 , wherein the sample subjected to MS analysis is first analyzed by a liquid chromatography (LC) system. 
     
     
       13. The method of  claim 11 , wherein the drug sample comprises pharmaceutical agents formulated with polymeric emulsifying agents. 
     
     
       14. The method of  claim 11 , wherein the specified first mass defect filter range is scalable in relation to mass over an initial mass range. 
     
     
       15. The method of  claim 14 , wherein the mass defect over the first mass defect filter range increases with increased mass. 
     
     
       16. The method of  claim 15 , wherein the mass defect increase is linear. 
     
     
       17. The method of  claim 15 , wherein the mass defect increase is non-linear and is based on determining a relationship between the mass defect range and the mass. 
     
     
       18. The method of  claim 14  further comprising:
 specifying a second mass defect filter range over another mass range. 
 
     
     
       19. The method of  claim 18  wherein the second mass defect filter range is a constant value. 
     
     
       20. The method of  claim 18  wherein the second range mass defect filter range is scalable in relation to mass. 
     
     
       21. The method of  claim 11  wherein the drug sample is a biological sample selected from plasma, bile, urine, fecal extract, bodily fluid or tissue samples. 
     
     
       22. The method of  claim 11 , wherein the impurities in the drug sample comprise degradants. 
     
     
       23. A system for detecting and identifying impurities in pharmaceutical samples, said system comprising:
 a high resolution mass spectrometer to detect ions of the impurities; 
 a processor configured to execute instructions which cause the system to perform a method comprising: 
 determining mass defect values for ions detected from said analysis; 
 specifying a range for mass defect values comprising a mass defect filter range; 
 comparing mass defect values of detected ions of the impurities within the specified range; 
 retaining mass defect values of ions of the impurities falling within the specified range; and 
 determining impurities from the retained values. 
 
     
     
       24. The system of  claim 23 , wherein retaining mass defect values occurs in a computer memory. 
     
     
       25. A system for detecting and identifying drug metabolites in biological samples, said system comprising:
 a high resolution mass spectrometer to detect ions of the metabolites; 
 a processor configured to execute instructions which cause the system to perform a method comprising: 
 determining mass defect values for ions detected from said analysis; 
 specifying a range for mass defect values comprising a mass defect filter range; 
 comparing mass defect values of detected ions of the metabolites within the specified range; 
 retaining mass defect values of ions of the impurities falling within the specified range; and 
 determining metabolites from the retained values. 
 
     
     
       26. A computer readable medium containing executable instructions which, when executed in a processing system, cause the system to perform a method comprising:
 subjecting a biological sample to a high resolution mass spectrometry (MS) analysis to detect ions; 
 detecting the ionic masses of ions from said analysis, said ionic masses forming an initial mass range; 
 determining mass defect values for the detected ions in the initial mass range; 
 specifying a range for a mass defect value comprising a mass defect filter; 
 discarding detected ions having mass defect values outside the mass defect filter range; 
 retaining detected ions having mass defect values within the mass defect filter range; and 
 determining species of interest from the retained ions to detect and identify drug metabolites in the biological sample.